Joan M. Skelly

Effect of Occult Metastases on Survival in Node-Negative Breast Cancer

BACKGROUND Retrospective and observational analyses suggest that occult lymph-node metastases are an important prognostic factor for disease recurrence or survival among patients with breast cancer. Prospective data on clinical outcomes from randomized trials according to sentinel-node involvement have been lacking. METHODS We randomly assigned women with breast cancer to sentinel-lymph-node biopsy plus axillary dissection or sentinel-lymph-node biopsy alone. Paraffin-embedded tissue blocks of sentinel lymph nodes obtained from patients with pathologically negative sentinel lymph nodes were centrally evaluated for occult metastases deeper in the blocks. Both routine staining and immunohistochemical staining for cytokeratin were used at two widely spaced additional tissue levels. Treating physicians were unaware of the findings, which were not used for clinical treatment decisions. The initial evaluation at participating sites was designed to detect all macrometastases larger than 2 mm in the greatest dimension. RESULTS Occult metastases were detected in 15.9% (95% confidence interval [CI], 14.7 to 17.1) of 3887 patients. Log-rank tests indicated a significant difference between patients in whom occult metastases were detected and those in whom no occult metastases were detected with respect to overall survival (P=0.03), disease-free survival (P=0.02), and distant-disease-free interval (P=0.04). The corresponding adjusted hazard ratios for death, any outcome event, and distant disease were 1.40 (95% CI, 1.05 to 1.86), 1.31 (95% CI, 1.07 to 1.60), and 1.30 (95% CI, 1.02 to 1.66), respectively. Five-year Kaplan-Meier estimates of overall survival among patients in whom occult metastases were detected and those without detectable metastases were 94.6% and 95.8%, respectively. CONCLUSIONS Occult metastases were an independent prognostic variable in patients with sentinel nodes that were negative on initial examination; however, the magnitude of the difference in outcome at 5 years was small (1.2 percentage points). These data do not indicate a clinical benefit of additional evaluation, including immunohistochemical analysis, of initially negative sentinel nodes in patients with breast cancer. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003830.).

Morbidity results from the NSABP B‐32 trial comparing sentinel lymph node dissection versus axillary dissection

Three year post‐surgical morbidity levels were compared between patients with negative sentinel lymph node dissection alone (SLND) and those with negative sentinel node dissection and negative axillary lymph node dissection (ALND) in the NSABP B‐32 trial.

Internet delivered behavioral obesity treatment

OBJECTIVES To evaluate the efficacy of an Internet behavioral weight loss program; and determine if adding periodic in-person sessions to an Internet intervention improves outcomes. METHODS 481 healthy overweight adults (28% minority) were randomized to one of 3 delivery methods of a behavioral weight loss program with weekly meetings: Internet (n=161), InPerson (n=158), or Hybrid (Internet+InPerson, n=162). Outcome variables were weight at baseline and 6 months and percent of subjects achieving a 5 and 7% weight loss. The study took place in two centers in Vermont and Arkansas from 2003 to 2008. RESULTS Conditions differed significantly in mean weight loss [8.0 (6.1) kg vs. 5.5 (5.6) kg vs. 6.0 (5.5) kg], for InPerson, Internet, and Hybrid respectively, p<0.01, n=462). Weight loss for InPerson was significantly greater than the Internet and Hybrid conditions (p<0.05). Although the proportion reaching a 5% weight loss did not differ, the proportion losing 7% did differ significantly (56.3% vs. 37.3% vs. 44.4% for InPerson, Internet, and Hybrid respectively, p<0.01). CONCLUSIONS These results demonstrate that the Internet is a viable alternative to in-person treatment for the delivery and dissemination of a behavioral weight-control intervention. The addition of periodic in-person sessions did not improve outcomes.

The Relationship Between Menstrual Cycle Phase and Anterior Cruciate Ligament Injury A Case-Control Study of Recreational Alpine Skiers

Background Female athletes suffer a greater incidence of anterior cruciate ligament tears compared with male athletes when participating in common sports; however, very little is known about the factors that explain this disparity. Study Design Case-control study; Level of evidence, 3. Methods Female recreational alpine skiers with an anterior cruciate ligament rupture and age-matched control skiers provided a serum sample and self-reported menstrual history data immediately after injury. Both serum concentrations of progesterone and menstrual history were then used to group subjects into either preovulatory or postovulatory phases of the menstrual cycle. Results Analysis of serum concentrations of progesterone revealed that alpine skiers in the preovulatory phase of the menstrual cycle were significantly more likely to tear their anterior cruciate ligaments than were skiers in the postovulatory phase (odds ratio, 3.22; 95% confidence interval, 1.09-9.52; P = .027). Analysis of menstrual history data found similar results, but the difference was not statistically significant (odds ratio, 2.38; 95% confidence interval, 0.86-6.54; P = .086). Conclusion The likelihood of sustaining an anterior cruciate ligament injury does not remain constant during the menstrual cycle; instead, the risk of suffering an anterior cruciate ligament disruption is significantly greater during the preovulatory phase of the menstrual cycle compared with the postovulatory phase. Clinical Relevance Phase of menstrual cycle may be one of the risk factors that influence knee ligament injury among female alpine skiers. The findings from this study should be considered in subsequent studies designed to identify persons at risk for anterior cruciate ligament injury and to develop intervention strategies.

Delay Discounting is Associated with Treatment Response among Cocaine-Dependent Outpatients

Delay discounting (DD) describes the rate at which reinforcers lose value as the temporal delay to their receipt increases. Steeper discounting has been positively associated with vulnerability to substance use disorders, including cocaine use disorders. In the present study, we examined whether DD of hypothetical monetary reinforcers is associated with the duration of cocaine abstinence achieved among cocaine-dependent outpatients. Participants were 36 adults who were participating in a randomized controlled trial examining the efficacy of voucher-based contingency management (CM) using low-magnitude (N = 18) or high-magnitude (N = 18) voucher monetary values. DD was associated with the number of continuous weeks of cocaine abstinence achieved, even after adjusting for treatment condition during the initial 12-week, t(33) = 2.48, p = .045 and entire recommended 24-week of treatment, t(33) = 2.40, p = .022. Participants who exhibited steeper discounting functions achieved shorter periods of abstinence in the Low-magnitude voucher condition (12-week: t(16) = 2.48, p = .025; 24-week: t(16) = 2.68, p = .017), but not in the High-magnitude voucher condition (12-week: t(16) = 0.51, p = .618; 24-week: t(16) = 1.08, p = .298), although the interaction between DD and treatment condition was not significant (12-week: t(32) = -1.12, p = .271; 24-week: t(32) = -0.37, p = .712). These results provide further evidence on associations between DD and treatment response and extend those observations to a new clinical population (i.e., cocaine-dependent outpatients), while also suggesting that a more intensive intervention like the High-magnitude CM condition may diminish this negative relationship between DD and treatment response.

Comparing Screening Mammography for Early Breast Cancer Detection in Vermont and Norway

BACKGROUND Most screening mammography in the United States differs from that in countries with formal screening programs by having a shorter screening interval and interpretation by a single reader vs independent double reading. We examined how these differences affect early detection of breast cancer by comparing performance measures and histopathologic outcomes in women undergoing opportunistic screening in Vermont and organized screening in Norway. METHODS We evaluated recall, screen detection, and interval cancer rates and prognostic tumor characteristics for women aged 50-69 years who underwent screening mammography in Vermont (n = 45 050) and in Norway (n = 194 430) from 1997 through 2003. Rates were directly adjusted for age by weighting the rates within 5-year age intervals to reflect the age distribution in the combined data and were compared using two-sided Z tests. RESULTS The age-adjusted recall rate was 9.8% in Vermont and 2.7% in Norway (P < .001). The age-adjusted screen detection rate per 1000 woman-years after 2 years of follow-up was 2.77 in Vermont and 2.57 in Norway (P = .12), whereas the interval cancer rate per 1000 woman-years was 1.24 and 0.86, respectively (P < .001). Larger proportions of invasive interval cancers in Vermont than in Norway were 15 mm or smaller (55.9% vs 38.2%, P < .001) and had no lymph node involvement (67.5% vs 57%, P = .01). The prognostic characteristics of all invasive cancers (screen-detected and interval cancer) were similar in Vermont and Norway. CONCLUSION Screening mammography detected cancer at about the same rate and at the same prognostic stage in Norway and Vermont, with a statistically significantly lower recall rate in Norway. The interval cancer rate was higher in Vermont than in Norway, but tumors that were diagnosed in the Vermont women tended to be at an earlier stage than those diagnosed in the Norwegian women.

Knowledge about preventing and managing lymphedema: a survey of recently diagnosed and treated breast cancer patients

Physical therapists, books and oncologists staff were the most frequently cited sources of lymphedema prevention and management information in a telephone survey of 148 recently treated breast cancer patients. Awareness, current practice and intention to practice 13 recommended prevention behaviors were low, and variations in these indices and in information sources were observed between those reporting any swelling and those who did not. Citing radiation oncologists as an information source reflected significantly higher levels of awareness, practice and intention as compared to not citing them. Also, citing oncologists reflected lower scores on the three indices as compared to not citing them. The results suggest that lymphedema prevention and management information is not getting to breast cancer survivors in a timely fashion and underscore the urgent need to develop and implement appropriate educational strategies. Additionally, research into factors that could motivate survivors to practice the recommended behaviors is warranted.

Effects of smoking cessation with voucher-based contingency management on birth outcomes.

AIMS This study examined whether smoking cessation using voucher-based contingency management (CM) improves birth outcomes. DESIGN Data were combined from three controlled trials. SETTING Each of the trials was conducted in the same research clinic devoted to smoking and pregnancy. PARTICIPANTS Participants (n=166) were pregnant women who participated in trials examining the efficacy of voucher-based CM for smoking cessation. Women were assigned to either a contingent condition, wherein they earned vouchers exchangeable for retail items by abstaining from smoking, or to a non-contingent condition where they received vouchers independent of smoking status. MEASUREMENT Birth outcomes were determined by review of hospital delivery records. FINDINGS Antepartum abstinence was greater in the contingent than non-contingent condition, with late-pregnancy abstinence being 34.1% versus 7.4% (P<0.001). Mean birth weight of infants born to mothers treated in the contingent condition was greater than infants born to mothers treated in the non-contingent condition (3295.6 ± 63.8 g versus 3093.6 ± 67.0 g, P = 0.03) and the percentage of low birth weight (<2500 g) deliveries was less (5.9% versus 18.5%, P = 0.02). No significant treatment effects were observed across three other outcomes investigated, although each was in the direction of improved outcomes in the contingent versus the non-contingent condition: mean gestational age (39.1 ± 0.2 weeks versus 38.5 ± 0.3 weeks, P = 0.06), percentage of preterm deliveries (5.9 versus 13.6, P = 0.09), and percentage of admissions to the neonatal intensive care unit (4.7% versus 13.8%, P = 0.06). CONCLUSIONS These results provide evidence that smoking-cessation treatment with voucher-based CM may improve important birth outcomes.

Educational disadvantage and cigarette smoking during pregnancy.

This study examined the influence of education on smoking status in a cohort (n=316) of pregnant women who were smokers at the time they learned of the current pregnancy. Subjects were participants in clinical trials examining the efficacy of monetary-based incentives for smoking-cessation and relapse prevention. In multivariate analyses, educational achievement was a robust predictor of smoking status upon entering prenatal care, of achieving abstinence antepartum among those still smoking at entry into prenatal care, and of smoking status at 6-month postpartum in the entire cohort and the subsample who received smoking-cessation treatment. In addition to educational attainment, other predictors of smoking status included smoking-related characteristics (e.g., number of cigarettes/day smoked pre-pregnancy), treatment, maternal age, and stress ratings. We suggest that strategies to increase educational attainment be included with more conventional tobacco-control policies in efforts to reduce smoking among girls and young women.

Reproducibility of BI-RADS breast density measures among community radiologists: a prospective cohort study.

Abstract:  Using data from the Vermont Breast Cancer Surveillance System (VBCSS), we studied the reproducibility of Breast Imaging Reporting and Data System (BI‐RADS) breast density among community radiologists interpreting mammograms in a cohort of 11,755 postmenopausal women. Radiologists interpreting two or more film‐screen screening or bilateral diagnostic mammograms for the same woman within a 3‐ to 24‐month period during 1996–2006 were eligible. We observed moderate‐to‐substantial overall intra‐rater agreement for use of BI‐RADS breast density in clinical practice, with an overall intra‐radiologist percent agreement of 77.2% (95% confidence interval (CI), 74.5–79.5%), an overall simple kappa of 0.58 (95% CI, 0.55–0.61), and an overall weighted kappa of 0.70 (95% CI, 0.68–0.73). Agreement exhibited by individual radiologists varied widely, with intra‐radiologist percent agreement ranging from 62.1% to 87.4% and simple kappa ranging from 0.19 to 0.69 across individual radiologists. Our findings underscore the need for additional evaluation of the BI‐RADS breast density categorization system in clinical practice.